Comparison of HIV prevalence, incidence, and viral load suppression in Zambia population-based HIV impact assessments from 2016 and 2021.

BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.

Prevalence and characteristics of metabolic syndrome and its components among adults living with and without HIV in Nigeria: a single-center study.

BACKGROUND: Persons living with HIV (PLHIV) now live longer due to effective combination antiretroviral therapy. However, emerging evidence indicates that they may be at increased risk for some cardiometabolic disorders. We compared the prevalence of metabolic syndrome (MetS) and its component disorders between persons living with and without HIV in Nigeria. METHODS: This was a cross-sectional analysis of baseline data from a prospective cohort study of non-communicable diseases among PLHIV along with age- and sex-matched persons without HIV (PWoH) at the University of Abuja Teaching Hospital Nigeria. We collected sociodemographic and clinical data, including anthropometric measures and results of relevant laboratory tests. MetS was defined using a modification of the third report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria. RESULTS: Of the 440 PLHIV and 232 PWoH, women constituted 50.5% and 51.3% respectively. The median age of the PLHIV was 45 years while that of the PWoH was 40 years. The prevalence of MetS was 30.7% (95% CI: 26.4%, 35.2%) and 22.8% (95% CI: 17.6%, 28.8%) among the PLHIV and PWoH respectively (P = 0.026). Independent associations were found for older age (P < 0.001), female sex (P < 0.001), family history of diabetes (P < 0.001), family history of hypertension (P = 0.013) and alcohol use (P = 0.015). The prevalence of component disorders for PLHIV versus PWoH were as follows: high blood pressure (22.3% vs 20.3%), prediabetes (33.8% vs 21.1%), diabetes (20.5% vs 8.2%), high triglycerides (24.5% vs 17.2%), low HDL-Cholesterol (51.1% vs 41.4%), and abdominal obesity (38.4% vs 37.1%). Adjusting for age and sex, prediabetes, diabetes, and low HDL-Cholesterol were significantly associated with HIV status. Duration on antiretroviral therapy, protease inhibitor-based regimen, CD4 count, and viral load were associated with some of the disorders mostly in unadjusted analyses. CONCLUSION: We found a high burden of MetS and its component disorders, with significantly higher prevalence of dysglycemia and dyslipidemia among PLHIV as compared to PWoH. Integration of strategies for the prevention and management of MetS disorders is needed in HIV treatment settings.

Expression profiling of human milk derived exosomal microRNAs and their targets in HIV-1 infected mothers.

Despite the use of antiretroviral therapy (ART) in HIV-1 infected mothers approximately 5% of new HIV-1 infections still occur in breastfed infants annually, which warrants for the development of novel strategies to prevent new HIV-1 infections in infants. Human milk (HM) exosomes are highly enriched in microRNAs (miRNAs), which play an important role in neonatal immunity. Furthermore, HM exosomes from healthy donors are known to inhibit HIV-1 infection and transmission; however, the effect of HIV-1 on HM exosomal miRNA signatures remains unknown. In this study, we used nCounter NanoString technology and investigated miRNAs expression profiles in first week postpartum HM exosomes from HIV-1 infected and uninfected control mothers (n = 36). Our results indicated that HIV-1 perturbed the differential expression patterns of 19 miRNAs (13 upregulated and 6 downregulated) in HIV-1 infected women compared to healthy controls. DIANA-miR functional pathway analyses revealed that multiple biological pathways are involved including cell cycle, pathways in cancer, TGF-ß signaling, FoxO signaling, fatty acid biosynthesis, p53 signaling and apoptosis. Moreover, the receiver operating characteristics (ROC) curve analyses of miR-630 and miR-378g yielded areas under the ROC curves of 0.82 (95% CI 0.67 to 0.82) and 0.83 (95% CI 0.67 to 0.83), respectively highlighting their potential to serve as biomarkers to identify HIV-1 infection in women. These data may contribute to the development of new therapeutic strategies in prevention of mother-to-child transmission (MTCT) of HIV-1.

Elevated Plasma Levels of sCD14 and MCP-1 Are Associated With HIV Associated Neurocognitive Disorders Among Antiretroviral-Naive Individuals in Nigeria.

BACKGROUND: Mononuclear cells play key roles in the pathogenesis of HIV-associated neurocognitive disorders (HAND). Limited studies have looked at the association of markers of monocyte activation with HAND in Africa. We examined this association among HIV-1-infected patients in Nigeria. METHOD: A total of 190 HIV-infected treatment-naive participants with immune marker data were included in this cross-sectional study. Plasma levels of soluble CD14 (sCD14), soluble CD163, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and neopterin were measured. Demographically adjusted T scores obtained from a 7-domain neuropsychological test battery were generated, and functional status was assessed using activities of daily living questionnaire. Participants were classified as unimpaired, having asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD) in line with the "Frascati" criteria. RESULTS: Thirty-two participants (16.8%) had ANI, 14 (7.4%) had MND, whereas none had HAD. In multivariable linear regression analyses, after adjusting for age, gender, education, CD4 count, and viral load, mean levels of sCD14 were higher among those with ANI and MND as compared with the unimpaired (P = 0.033 and 0.023, respectively). Similarly, the mean level of MCP-1 was greater among those with HAND as compared with the unimpaired (P = 0.047). There were also trends for higher levels of sCD163 and TNF-α among females with MND in univariable analyses. CONCLUSIONS: Levels of monocyte activation markers correlate with the severity of impairment among individuals with HAND. The mechanisms that underlie these effects and the potential role of gender require further study.

Missed opportunities for early infant diagnosis of HIV in rural North-Central Nigeria: A cascade analysis from the INSPIRE MoMent study.

BACKGROUND: Early identification of HIV-infected infants for treatment is critical for survival. Efficient uptake of early infant diagnosis (EID) requires timely presentation of HIV-exposed infants, same-day sample collection, and prompt release of results. The MoMent (Mother Mentor) Nigeria study investigated the impact of structured peer support on EID presentation and maternal retention. This cascade analysis highlights missed opportunities for EID and infant treatment initiation during the study. METHODS: HIV-infected pregnant women and their infants were recruited at 20 rural Primary Healthcare Centers. Routine infant HIV DNA PCR testing was performed at centralized laboratories using dried blood spot (DBS) samples ideally collected by age two months. EID outcomes data were abstracted from study case report forms and facility registers. Descriptive statistics summarized gaps and missed opportunities in the EID cascade. RESULTS: Out of 497 women enrolled, delivery data was available for 445 (90.8%), to whom 415 of 455 (91.2%) infants were live-born. Out of 408 live-born infants with available data, 341 (83.6%) presented for DBS sampling at least once. Only 75.4% (257/341) were sampled, with 81.7% (210/257) sampled at first presentation. Only 199/257 (77.4%) sampled infants had results available up to 28 months post-collection. Two (1.0%) of the 199 infants tested HIV-positive; one infant died before treatment initiation and the other was lost to follow-up. CONCLUSIONS: While nearly 85% of infants presented for sampling, there were multiple missed opportunities, largely due to health system and not necessarily patient-level failures. These included infants presenting without being sampled, presenting multiple times before samples were collected, and getting sampled but results not forthcoming. Finally, neither of the two HIV-positive infants were linked to treatment within the follow-up period, which may have led to the death of one. To facilitate patient compliance and HIV-free infant survival, quality improvement approaches should be optimized for EID commodity availability, consistent DBS sample collection, efficient processing/result release, and prompt infant treatment initiation.

Development, Evaluation, and Implementation of a Pan-African Cancer Research Network: Men of African Descent and Carcinoma of the Prostate.

PURPOSE: Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. METHODS: We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. RESULTS: We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. CONCLUSION: We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Addressing the under-reporting of adverse drug reactions in public health programs controlling HIV/AIDS, Tuberculosis and Malaria: A prospective cohort study.

BACKGROUND: Adverse Drug Reactions (ADRs) are a major clinical and public health problem world-wide. The prompt reporting of suspected ADRs to regulatory authorities to activate drug safety surveillance and regulation appears to be the most pragmatic measure for addressing the problem. This paper evaluated a pharmacovigilance (PV) training model that was designed to improve the reporting of ADRs in public health programs treating the Human Immunodeficiency Virus (HIV), Tuberculosis (TB) and Malaria. METHODS: A Structured Pharmacovigilance and Training Initiative (SPHAR-TI) model based on the World Health Organization accredited Structured Operational Research and Training Initiative (SOR-IT) model was designed and implemented over a period of 12 months. A prospective cohort design was deployed to evaluate the outcomes of the model. The primary outcomes were knowledge gained and Individual Case Safety Reports (ICSR) (completed adverse drug reactions monitoring forms) submitted, while the secondary outcomes were facility based Pharmacovigilance Committees activated and health facility healthcare workers trained by the participants. RESULTS: Fifty-five (98%) participants were trained and followed up for 12 months. More than three quarter of the participants have never received training on pharmacovigilance prior to the course. Yet, a significant gain in knowledge was observed after the participants completed a comprehensive training for six days. In only seven months, 3000 ICSRs (with 100% completeness) were submitted, 2,937 facility based healthcare workers trained and 46 Pharmacovigilance Committees activated by the participants. Overall, a 273% increase in ICSRs submission to the National Agency for Food and Drug Administration and Control (NAFDAC) was observed. CONCLUSION: Participants gained knowledge, which tended to increase the reporting of ADRs. The SPHAR-TI model could be an option for strengthening the continuous reporting of ADRs in public health programs in resource limited settings.

Associations between Cognition, Gender and Monocyte Activation among HIV Infected Individuals in Nigeria.

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes.

Soluble toll-like receptor 2 is significantly elevated in HIV-1 infected breast milk and inhibits HIV-1 induced cellular activation, inflammation and infection.

OBJECTIVES: We previously demonstrated that immunodepletion of soluble Toll-like receptor 2 (sTLR2) from human breast milk significantly increased HIV infection in vitro. The aims of this study were to characterize sTLR2 levels in breast milk from HIV-infected and uninfected women, and identify a mechanism by which sTLR2 inhibits HIV-induced cellular activation and infection. DESIGN: Blinded studies of breast milk from HIV-infected and uninfected Nigerian and Canadian women were evaluated for levels of sTLR2, proinflammatory cytokines and viral antigenemia. In-vitro experiments were conducted using cell lines to assess sTLR2 function in innate responses and effect on HIV infection. RESULTS: Breast milk from HIV-infected women showed significantly higher levels of sTLR2 than uninfected breast milk. Further, sTLR2 levels correlated with HIV-1 p24 and interleukin (IL)-15, thus suggesting a local innate compensatory response in the HIV-infected breast. Given the significantly higher levels of sTLR2 in breast milk from HIV-infected women, we next demonstrated that mammary epithelial cells and macrophages, which are prevalent in milk, produced significantly increased levels of sTLR2 following exposure to HIV-1 proteins p17, p24 and gp41 or the TLR2 ligand, Pam3CSK4. Our results also demonstrated that sTLR2 physically interacts with p17, p24 and gp41 and inhibits HIV-induced nuclear factor kappa-light-chain-enhancer of activated B cells activation, and inflammation. Importantly, binding of sTLR2 to HIV-1 proteins inhibited a TLR2-dependent increase in chemokine receptor 5 expression, thus resulting in significantly reduced HIV-1 infection. CONCLUSION: These results indicate novel mechanisms by which sTLR2 plays a critical role in inhibiting mother-to-child HIV transmission.

Reference values of CD4 T lymphocytes in human immunodeficiency virus-negative adult Nigerians.

A cross-sectional study that involved secondary analysis of data collected from 681 pregnant women and 183 miners (94 men and 89 women; ratio of men to women, 1:0.95) in Jos, Nigeria, was carried out to determine the reference ranges for CD4(+)-cell counts in healthy HIV-negative adult Nigerians. The main results of interest were CD4(+)-cell counts and odds ratios (ORs) of low CD4(+)-cell counts, defined as below 350 cells per microl. CD4(+)-cell counts were similar in men and nonpregnant women, with a mean (standard deviation) of 828 (203) cells per microl, but pregnant women had a lower value of 771 (250) cells per microl. None of the factors assessed was related to the odds of having a low CD4(+)-cell count among men and nonpregnant women, but age, age of marriage, and alcohol usage were significant predictors in pregnant women. Compared to pregnant women less than 20 years old, older women had significantly lower odds of a low CD4(+)-cell count (ORs were 0.06 for women aged 20 to 29 years and 0.22 for those aged 30 to 39 years). When compared with those pregnant women who were married before 20 years of age, those who married at 20 to 29 years and 30 to 39 years had odds ratios of 6.41 and 9.40, respectively. Previous alcohol use was also associated with low CD4(+)-cell counts (OR, 5.15). The 95% confidence interval for CD4(+)-cell counts in healthy adult Nigerians is 547 to 1,327 cells per microl, and this is the first time this has been determined.